Antioxidants enhance the recovery of three cycles of bleomycin, etoposide, and cisplatin-induced testicular dysfunction, pituitary-testicular axis, and fertility in rats

Objective To investigate the effects of an antioxidant cocktail (AC) on bleomycin, etoposide, and cisplatin (BEP)-induced testicular dysfunction. Design In vivo study. Setting Research laboratory. Animal(s) Adult male and female Sprague-Dawley rats. Intervention(s) The rats were treated with three cycles of 21 days each of therapeutically relevant dose levels of BEP (0.75, 7.5, and 1.5 mg/kg) with or without the AC (a mixture of α-tocopherol, L-ascorbic acid, Zn, and Se). Main Outcome Measure(s) Sperm parameters, fertility, serum hormone levels (ELISA), testicular histopathology, and expression of proliferating cell nuclear antigen (PCNA), and transferrin (Western blotting and immunohistochemistry) were evaluated at the end of treatment and a 63-day recovery period. Result(s) At the end of treatment, the AC improved BEP-induced decrease in sperm motility and increase in abnormality but had no effect on reduced sperm count, fertility, and tubular atrophy, although it up-regulated germ cell proliferation. The AC normalized reduced inhibin B levels, but had no effect on decreased transferrin and testosterone and elevated LH levels. At the end of the recovery period, the AC enhanced the expression of PCNA and transferrin, repopulation of germ cells, LH-testosterone axis, and fertility, but had no effect on reduced FSH and elevated inhibin B levels. Conclusion(s) The antioxidants protect and then enhance the recovery of testicular and reproductive endocrine functions when administered concomitantly with BEP therapy. The AC may be beneficial to regain testicular functions after chemotherapy.